Hydrogel and Silicone Hydrogel Lens Care

By Susan J. Gromacki, OD, MS, FAAO

The recent Fusarium and Acanthamoeba keratitis outbreaks as well as the related unprecedented, permanent recall of ReNu with MoistureLoc (Bausch & Lomb) and Complete MoisturePlus (Advanced Medical Optics) have brought a heightened awareness about contact lens care. Because of widespread coverage by the lay media, patients and practitioners alike have learned that solution composition and compliance do matter. In this climate, it has never been more important for practitioners to understand the care system components, to prescribe the proper care products for each individual patient and to strictly emphasize proper compliance with their chosen regimen. The role of contact lens care products remains the same as always: to remove surface deposition, to disinfect microorganisms and to improve surface wettability.

FDA Approval

A contact lens solution is a Class II device and must pass specific Food and Drug Administration (FDA) tests before it can be approved, labeled and sold in the United States. For example, a disinfection solution must undergo stand-alone and regimen testing.

Stand-alone testing evaluates only the disinfection solution and determines whether the solution can effectively kill certain microorganisms that are inoculated into it. The microorganisms include three bacteria (Staphylococcus aureus, Pseudomonas aeruginosa and Serratia marcescens) and two fungi (Candida albicans and Fusarium solani). For the stand-alone test the solution is required to reduce the bacteria by at least 3 log units of 1.0 × 10⁵ to 1.0 × 10⁶ colony forming units (cfu)/ml inoculum and the fungi by at least 1 log unit of 1.0 × 10⁵ to 1.0 × 10⁶ cfu/ml inoculum over the time period that the manufacturer has specified for disinfection.

The regimen test evaluates the disinfection solution and all other components of the total recommended cleaning and disinfection procedure, such as pre-cleaning solution, rinsing solution, rubbing or no rub, etc. The same organisms for the stand-alone procedure are used, as are selected contact lenses of various materials (the material[s] that the manufacturer seeks to gain approval for use with the solution regimen being tested). Lenses are then cleaned, rinsed and soaked in the manufacturer's recommended manner. After soaking, the lenses are analyzed to determine microbial growth. The requirements for bacteria are a minimum of 1 log reduction of each organism and a minimum of 5 log reduction of a sum of the averages for all organisms as well as less than 10 cfu following the cleaning/soaking regimen. The requirements for fungi are stasis of each organism and less than 10 cfu following the cleaning/soaking regimen.

In addition to tests for disinfection efficacy, the FDA uses other tests such as one for cleaning efficacy. Also, the FDA uses the disinfection test and other tests whether for a single bottle of solution or for a system that uses a combination of separate bottles of solution with specific purposes, such as for cleaning, rinsing and disinfecting. Obviously, a multipurpose solution (MPS) must satisfy the same efficacy criteria with its one solution as would a system of separate solutions for specific purposes.

A solution must show a "substantial equivalency" to comparable products previously approved. In other words, it must be as safe and effective as these other solutions for the same usage or function. Assuming the solution under-going testing has similar chemical components and percentages as that of already approved solutions, any required clinical testing may need only 30 subjects for 30 days.

If the chemical components are new or different percentages, the same in vitro testing is required. However, the clinical testing is more extensive and may require about 60 subjects for 90 days.

Chemical Disinfection

Chemical disinfection utilizes either preservatives or hydrogen peroxide to eliminate microorganisms. They were once two- to three-bottle care systems, but today almost all of the leading chemical disinfectants are multipurpose (MPS) one-bottle systems. To facilitate proper disinfection and storage, these solutions contain a complex combination of ingredients.

Ingredients Cleaners/surfactants remove mucin, debris, contaminants and makeup, which helps maintain a clean, wettable lens surface. Cleaners/surfactants may comprise part of an MPS (such as borate and citrate) or can stand alone as daily cleaners. For example, isopropyl alcohol (MiraFlow Extra-Strength Cleaner, CIBA Vision) is especially good at dissolving lipids. Surfactant cleaners are generally present in low amounts as part of an MPS, while separately packaged cleaning solutions have a greater concentration and use a red cap to indicate that patients should not place them directly onto the eye. However, with thorough rinsing from the lens, cleaners usually do not cause hypersensitivity reactions.

Preservatives are antimicrobial agents such as polyaminopropyl biguanide, polyhexanide hydrochloride, polyquaternium-1 and myristamidopropyl dimethylamine. First-generation preservatives such as thimerosal or chlorhexidine, when used in higher concentrations, caused hypersensitivity reactions. Today's preservatives have higher molecular weights and tend not to penetrate the matrices of soft contact lenses, which reduces sensitivity reactions. However, some sensitive patients can still develop allergic or toxic reactions to preservatives.

Buffers keep the pH of the solution close to that of natural tears, enhancing compatibility. They also can aid in cleaning and disinfection. Common buffers include sodium borate and boric acid.

Lubricants, or wetting agents, decrease the wetting angle of the contact lens material. Good wettability is especially important because the primary reason for contact lens dropout is discomfort from dryness. Examples of lubricants include hydroxypropyl methylcellulose, Tetronic 1304, C9-ED3A and poloxamine.

Chelators such as edetate disodium (EDTA) prevent calciumbound proteins from depositing on the lens surface, which enhances disinfection.

Protein removers are another component of lens care systems. Historically, proteolytic enzymes removed protein from lens surfaces whereby a separate enzyme tablet was dissolved in the contact lens soaking solution. Today, this step is usually reserved for lenses prescribed for more than one month of wear. Two brands remain: Ultrazyme (AMO) and Unizyme (CIBA Vision). Both contain subtilisin A. Alternatively, patients can utilize a daily protein remover such as Opti-Free SupraClens (Alcon). Many MPSs contain built-in non-enzymatic protein removers, as enzymes can irritate the eyes. For example, hydroxyalkyl phosphonate ("Hydranate") in ReNu MultiPlus (Bausch & Lomb) serves as a chelating agent that ionically removes protein from the lens surface. Sodium citrate in the Opti-Free products (Alcon) is a negatively charged molecule that attracts positively charged protein molecules from the lens surface.

MPSs represent the most popular mode of disinfection today (Table 1). These one-bottle systems include most of the solution components discussed and usually allow storage for up to 30 days in an unopened case without needing to change the solution.

Opti-Free Replenish is the newest MPS available. Along with Opti-Free Express, it's a multipurpose disinfecting solution (MPDS). Like Opti-Free Express, it contains Polyquad (polyquaternium-1) and Aldox as disinfectants and citrate for cleaning (Table 2). Additionally, it includes "TearGlyde" (Tetronic 1304 and C9-ED3A) as a wetting agent. This additive gives the solution FDA-approved labeling claims for retaining moisture and reconditioning lenses for enhanced comfort. It has no-rub approval and a six-hour required soak time for disinfection.

ReNu MultiPlus has once again become B&L's premium MPS since the permanent removal of ReNu with MoistureLoc from the market. The chlorhexidine derivative polyaminopropyl biguanide (PHMB) 0.0001% ("Dymed") serves as the preservative for ReNu MultiPlus. Its cleaner is poloxamine and its protein remover is hydroxyalkyl phosphonate. It has no-rub approval. Lenses require a four-hour soak for disinfection.

Complete Multi-Purpose Solution Easy Rub Formula (AMO) is another older formulation resurrected to replace Complete MoisturePlus after its permanent recall. The primary disinfectant is polyhexamethylene biguanide 0.0001% ("TrisChem"), another chlorhexidine derivative. Phosphate serves as the cleaner and Poloxamer 237 as the wetting agent. This formulation has no-rub approval, but is packaged and marketed to require a 10-second rub followed by a five-second rinse. After soaking at least six hours to disinfect, package instructions specify an additional rinse for five seconds per side.

Aquify is CIBA Vision's premium MPS offering. Polyhexanide serves as the disinfectant, with Dexpant-5 and sorbitol ("HydroLock") as wetting/comfort agents. With the no-rub instructions, including the rinse, disinfection takes four hours. With a 10-second digital rub, disinfection takes only five minutes.

Sauflon Pharmaceuticals' All In One Lite no-rub MPS contains poloxamer, sodium phosphate as a buffer, disodium edetate and is preserved with polyhexanide.

Hydrogen Peroxide Disinfectants Hydrogen peroxide (H₂O₂) penetrates hydrogel materials, providing a thorough cleaning by expanding the lens matrix and oxidizing microbes. Because of its hypotonic nature and an acidic pH of 4.00, it's also able to break protein and lipid bonds and remove trapped debris. In addition, it can penetrate microbial biofilms, which most multipurpose soft lens solutions can't do. It's also preservative-free — ideal for patients who have hypersensitivities or dry eye. H₂O₂ must be neutralized before placing lenses on the eyes.

AOSept (CIBA) is a three-bottle system that combines a potent daily cleaner with 3% H₂O₂ disinfection. MiraFlow is its daily cleaner and can emulsify lipids as well as provide some lens disinfection. The third bottle, Softwear saline, is needed to rinse off the MiraFlow prior to disinfection. Neutralization, performed with a platinumcoated plastic disc, takes six hours. Once disinfected, soft lenses can be safely stored for 24 hours.

Oxysept UltraCare Formula Peroxide Disinfection System (AMO) uses 3% H₂O₂ to disinfect lenses. Lens Plus Daily Cleaner and Saline, once a part of this care system, are now owned by Inyx/Exaeris. A daily cleaner and saline rinse are indicated with Oxysept, but no specific cleaner is part of the system. An advantage to this system is the presence of a wetting agent (hydroxypropyl methylcellulose, HPMC) in the neutralization tablet. AMO recommends that patients place lenses directly onto the eye in the morning so as not to rinse off the lubricant. The catalase tablet also includes cyanocobalamin (vitamin B₁₂), which creates a pink hue just before total neutralization (six hours) to indicate that the tablet was placed into the solution. Maximum storage time is seven days.

Clear Care (CIBA) combines a cleaner — Pluronic 17R4 — and 3% H₂O₂ in one bottle. With a five-second rinse, it's FDA-approved for no rub. It has a six-hour neutralization period (using a platinum-coated plastic disc) and is approved for seven days of storage.

Sauflon One Step combines hydrogen peroxide, a non-ionic surfactant cleaner and a lubricating agent to clean and disinfect lenses and enhance patient comfort.

Ultraviolet Light and Ultrasonic Disinfection

The PuriLens System (PuriLens, Inc.) utilizes a combination of subsonic cleaning and UV-C light to disinfect soft lenses. Using its own brand of preservative-free saline to soak the lenses, this electronic unit plugged into an outlet produces shear waves (creating a whirlpool effect) to remove debris from the lens and germicidal light that kills microorganisms by breaking nucleic acid bonds in their DNA. The cycle lasts 15 minutes.

Best Health, Inc. manufactures the LensComfort Ultrasonic Cleaning & Disinfecting System. This no-rub process involves placing lenses in the unit with LensComfort Multipurpose Solution and plugging the unit into an outlet. According to the company, the ultrasound and the antimicrobial MPS combine to kill both bacteria and fungi in about 15 minutes.

Silicone Hydrogels

Practitioners are fitting silicone hydrogel materials in record numbers — 82 percent select silicone hydrogel materials for new spherical contact lens patients. These materials impart considerably more oxygen than hydroxymethacrylate (HEMA) lenses, which results in fewer hypoxic complications. What we don't know completely, however, is how these materials react and perform with care products that were approved mostly before their availability. And what's more, the various silicone hydrogel materials are as different as they are alike.

In addition to increased oxygen permeability, the advantages of these materials over traditional hydrogels include better durability, less protein deposition and increased end-of-day comfort. Unlike HEMA-based soft polymers, they are innately hydrophobic; all but one available material — comfilcon A (Biofinity, CooperVision) — have to be surface-treated or contain an internal wetting agent for successful wear. Because silicone is more permeable to oxygen than is water (the opposite is true for traditional plastics), in general, the lower the water content, the higher the permeability. Potential drawbacks for some patients include increased lipid deposition and increased stiffness of some of the materials, reflected by higher modulus of elasticity values. Rarely, this increases the potential for mechanical irritation to the eye.

There are currently four care systems that are FDA-indicated for use with silicone hydrogels (Table 3). Other solutions may be compatible with silicone hydrogel materials. The FDA labeling indication represents the efforts of companies that comprehensively tested their products, reported their results to the FDA and demonstrated that their solutions don't alter the parameters of the lenses. (The FDA doesn't take compatibility with the ocular surface into account.) It's important to understand that when all of these solutions except Opti-Free Replenish were approved for this labeling, the only silicone hydrogel on the market was Night & Day (CIBA). Although the FDA hasn't required testing with the other materials to retain the labeling, there have been no reports of incompatibilities.

Until other care products undergo successful testing with silicone hydrogels, I instruct my patients that no substitutions are allowed, including generics/private-label. Generics are typically older, rather than premium, formulations and can change from year to year. But most importantly, few of the current generic solutions contain formulations indicated by the FDA for use with silicone hydrogels. With close to 50 percent of solutions being purchased from Wal-Mart, Target and KMart, the vast majority of private-label bottles currently contain ReNu MultiPlus.

Known Incompatibilities

There is currently one care system contraindication reported on a contact lens solution package insert: AMO's Oxysept UltraCare Formula is contraindicated with CIBA Vision's Illusions lenses.

The package insert for PureVision lenses states, "Do not use the Allergan Ultracare Disinfecting System or any of its components (Ultracare Disinfecting Solution, Ultracare Neutralizing Tablets, Lens Plus Daily Cleaner and Ultrazyme Enzymatic Cleaner) to clean and disinfect the PureVision Contact Lens." However, AMO states that Oxysept is not contraindicated with PureVision. Other hydrogen peroxide systems have demonstrated no incompatibilities with PureVision or with any other silicone hydrogel lenses.

Although not a labeled contraindication at this time, the combination of Renu MultiPlus with several soft lens materials, most notably with PureVision, causes corneal staining in some patients. Andrasko and Ryen have placed patients into 99 different lens and solution combinations (sample size 2,807) and checked patients for staining two hours after each lens/solution application for their staining grid study. They found that on average, 73 percent of the area of each patient's cornea stained after wearing the PureVision/ReNu MultiPlus combination (Figure 1). Numbers were similar for PureVision with the Wal-Mart and Target solutions because both are currently identical in composition to ReNu MultiPlus. Staining percentages were considerably lower for other lens/solution combinations. For example, Clear Care averaged just over 1 percent with all nine test lens materials, which was even lower than the control (unpreserved saline). Dumbleton's recent study found that in 55 patients who wore five different silicone hydrogel lenses, there were no cases of solution sensitivity staining associated with Clear Care.

Figure 1. Corneal staining in patient utilizing PureVision lenses and ReNu MultiPlus solution.

(Photo courtesy of Gary Andrasko, OD, www.StainingGrid.com.)

Although we don't completely understand the mechanism for how this staining occurs, some researchers propose that certain care products bind to lipid deposits on the silicone hydrogel lens surface, which then act as a drug delivery device. In addition, this staining is mostly asymptomatic and generally resolves at the four- to six-hour mark once the preservative has completely released from the lens.

No documented link currently exists between a two-hour time period of corneal disruption and microbial keratitis. It's nevertheless important to evaluate the cornea with sodium fluorescein and a yellow Wratten filter at every visit, whether the patient is symptomatic or not. It's important to be aware that solution/material interactions do exist and to always look for signs of potential problems.

Lessons Learned From the Fusarium and Acanthamoeba Keratitis Outbreaks

The Fusarium and Acanthamoeba keratitis outbreaks of 2006 and 2007, respectively, demonstrated to our patients that not all solutions are identical. The disproportionate number of affected patients who used ReNu with MoistureLoc and developed Fusarium keratitis (Figure 2) or who used Complete MoisturePlus and developed Acanthamoeba keratitis (Figure 3) led to the permanent worldwide recall of both solutions.

It was initially and inaccurately assumed that the culprit was MoistureLoc's preservative, alexidine. However, during noncompliant conditions such as if the solution was allowed to evaporate; if it was not regularly replaced in the lens case; if the bottle was kept open between uses; or if the case was not cleaned properly or replaced regularly, then "the concentration of the polymers included in the formula to enhance comfort may make the solution more likely to be contaminated with Fusarium in the environment," according to B&L. MoistureLoc contains a higher concentration of polymers than any other major lens care product. In other words, the wetting agents during noncompliant conditions encapsulated the Fusarium spores, allowing them to survive and germinate. Additional studies have demonstrated that other care products are less effective against Fusarium under sustained high-temperature conditions. The FDA doesn't require solution testing during adverse environments or during non-compliant care.

Figure 2. Fusarium keratitis: ReNu with MoistureLoc was recalled after being linked with this condition.

(Photo courtesy of Eduardo C. Alfonso, MD)

In addition, the FDA doesn't require testing of a solution's efficacy against amoebae. Research had previously demonstrated Complete MoisturePlus's diminished efficacy against Acanthamoeba.

Compliance Makes a Difference The Fusarium and Acanthamoeba keratitis outbreaks were due in part to patient noncompliance. Although the silicone hydrogel materials provide good oxygen transmission, they still need to be cleaned and disinfected. They deposit lipids more readily than do hydrogels. For this reason, specifically instruct your patients to rub their silicone hydrogel lenses even if the box and insert contain the words "no rub." Following the Fusarium outbreak, the FDA and the Centers for Disease Control and Prevention (CDC) also adopted recommending the "rub and rinse" rather than the no-rub cleaning method for all lenses. Most manufacturers agree and have been gradually decreasing the size of the words "no rub" on product packaging.

New research has demonstrated that adding a rub step to both multipurpose and peroxide systems reduces or even eliminates deposition problems on silicone hydrogel lenses, even in a deposit-prone population. I instruct patients that digital rubbing removes 90 percent of the debris and that the alternative (typically 10 seconds of rinsing prior to placing the lens in a solutionfilled case) is not only less healthy in some instances, but is also less economical.

One important lesson practitioners learned from the Acanthamoeba keratitis outbreak is to pay closer attention to case care. In April 2007, The American Optometric Association released specific instructions on preventing Acanthamoeba keratitis:

• Every day, mechanically scrub (using a clean washcloth or new toothbrush) the inside and outside of the contact lens case with sterile contact lens disinfecting solution.
• Avoid using tap water to wash or store lens cases.
• Air dry your lens case when not in use. Cover case with a clean towel. (Exception: the ProGuard case, used with Aquify solution, should remain closed to maintain its antimicrobial properties.)
• Replace the lens case every one to three months.

Another sequela of the outbreaks is the shifted responsibility of care system selection from ancillary staff member to practitioner. I believe practitioners now tend to carefully prescribe solutions based on their patients' lens material, wearing and replacement schedule and eye health. I delegate application, removal and care training to my technician, but only after I have selected the solution myself and reviewed it with my patients. This includes reading the package insert with them and requesting that they review it at home. Some practitioners also provide a handout listing the solution name, while others present the patient with a copy of his solution "prescription" on an Rx pad. Whatever the method, it has never been more vital to reinforce good compliance and to discourage patient deviation from your prescribed solution.

Figure 3. Acanthamoeba keratitis: Complete Moisture-Plus was recalled after being linked with this condition.

To prevent noncompliance and to ensure healthy contact lens wear for your patients, urge them to follow these instructions:

1. Always wash your hands with soap and water before handling contact lenses.
2. Wear and replace lenses according to the schedule prescribed.
3. Follow the specific lens cleaning and storage guidelines from your practitioner. Don't deviate from the lens care products your practitioner recommends.
4. Make sure you always use fresh solution; discard used solution and replace daily. If you don't use the lenses daily, follow the manufacturer's recommendations for cleaning and storing the lenses.
5. Do not swim, shower or use a hot tub while wearing lenses.
6. Remove your lenses and consult your practitioner immediately if you experience symptoms such as redness, pain, tearing, increased light sensitivity, blurry vision, discharge or swelling.

Conclusion

The use of appropriate solutions is an essential component of successful contact lens wear. Practitioners need to understand the technical aspects, and patients need to receive proper education and encouragement for compliance. CLS

Dr. Gromacki is a Diplomate in Cornea and Contact Lenses in the American Academy of Optometry. She has a specialty contact lens and post-surgical co-management practice as part of a multi-subspecialty ophthalmology group in Ann Arbor, MI.

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